Meet Mark

Let me introduce myself. My name is Mark Sisson. I’m 63 years young. I live and work in Malibu, California. In a past life I was a professional marathoner and triathlete. Now my life goal is to help 100 million people get healthy. I started this blog in 2006 to empower people to take full responsibility for their own health and enjoyment of life by investigating, discussing, and critically rethinking everything we’ve assumed to be true about health and wellness...

CRISPR: What Does Gene Editing Mean for the Future of Primal Living?

By now, you’ve no doubt heard of CRISPR, the latest gene-editing tool sweeping research labs across the globe. It was first discovered in certain strains of bacteria, who use it as an important weapon against dangerous viruses. In bacteria, CRISPR identifies a virus that poses a threat, records the virus’ genetic data and imprints it onto RNA molecules. An immune enzyme called Cas9 grabs one of the RNA molecules and goes exploring. When Cas9 encounters a virus that matches the data on the RNA molecule, it latches on and slices the virus in half to prevent it from replicating and posing any threat.

Researchers have co-opted the CRISPR/Cas9 mechanism to edit genes. Instead of copying dangerous viral DNA sequences onto the RNA molecules, they can copy over any sequence they want to edit. And instead of Cas9 destroying viruses, it makes precise cuts and removes specific bits of genetic data from the designated sequence. This allows researchers to target and edit specific gene sequences with genetic data of their choosing.

Are there risks?

“Off-target” events.

Although we know how to program Cas9 to make specific edits to genes, it’s not always accurate. Sometimes the wrong portion of the sequence is removed and replaced. Other times, Cas9 slices the right sequence but, once inside the cell, starts editing other sequences. Early CRISPR editing accuracy varied wildly, with some studies reporting many “off-target” events and others reporting very few. As you might imagine, editing the wrong genetic sequence defeats the purpose of CRISPR entirely and can even create new health conditions.

The latest updates to the CRISPR tech have made huge strides in accuracy. Using edited Cas9 enzymes from Strep. pyogenes, MIT and Harvard scientists have nearly abolished off-target events, as evidenced by a study from late last year.

Unforeseen “off-target” events.

Right now they use a composite human genome, a kind of “standard” or “template,” to map and avoid the potential off-target interactions. But in actual real people (or embryos), every genome is unique. No standardized genome map can account for that. So the predictive model that works so well in the lab on a homogeneous sample might not play out the same in the real world.

Assuming those get ironed out, what’s the prospect of hyper-intelligent designer babies?

First, the most alluring traits are the hardest to edit. Want a smarter kid? Dozens of genes contribute to cognitive ability (PDF), none contributing more than a couple IQ points. Height? Hundreds of genes contribute to height. Personality? Thousands.

I won’t go over every potentially beneficial edit we can make to our genes with CRISPR. You name a trait or disease and it can probably be modified with genetic editing. The environment and other epigenetic inputs matter too, of course, but genes underlie everything.

Okay.

Assuming we do figure it all out, identify all the SNPs that interact with the traits and conditions we want to edit, could CRISPR render Primal living, eating, and exercising moot?

After all, some people are just impervious to metabolic derangement. They’re set up for lifelong leanness, health, and longevity, mostly because of their genes. That can be replicated, assuming the technology works. If genetic editing turns every incoming human into that lucky jerk in your high school who sat around all day eating McDonald’s and never gained an ounce while dominating three varsity sports, many people will give up their gym memberships and stop shopping the produce aisle.

I’m sure, given enough time, scientists will figure out a way to edit genes so that we never have to exercise, watch what we eat, or worry about our health ever again. We’ll become superworkers, impervious to stress and able to function (and stay healthy) on three hours of sleep a night. We’ll have the option to become energy-wasting (eat all you want, whatever you want, never gain an ounce) or energy-conserving (thrive on a few hundred calories a day, never get hungry) organisms. We’ll be able to reduce our vitamin D requirements or enhance our vitamin D synthesis to the point where a minute of sunlight every week is plenty.

The foods, behaviors, exercises, and lifestyle factors that make us healthy aren’t purely utilitarian. And even if they are, we don’t see them that way. Evolutionary pressures work below the conscious level. The pleasure of sex incentivizes us to spread our genetic material. The spread of our genetic material is the proximate cause, but that’s not what motivates us in the moment. It’s the pleasure.

We may not have to practice “lots of slow moving,” but isn’t walking barefoot over grass or along the beach kinda nice?

We may never have to trail run through the redwoods, but damn if that isn’t a gorgeous, sacred way to spend an afternoon.

I don’t think those reactions to Primal practices go away.

If anything, people being able to ensure their health and fitness will allow them to focus on the pleasure, meaning, and fun the Primal lifestyle offers.

And there will be other edits we can make down the line that can enhance our quality of life and arguably make us even more Primal.

In resource-limited environments, like our ancestral backdrop, it made sense to have myostatin. Extra muscle required extra calories. We didn’t need to look like Terminator-era Arnold to be effective hunter-gatherers. These days, we don’t have to hunt or forage for our food. We just walk down to the market and buy whatever we want. It’s cheaper than ever before. We can eat about as much as we want. We can enjoy big muscles even if we don’t really need them.

I’m quite optimistic.

People tend to imagine the worst kind of dystopian cyberpunk future: genetic ubermensch striding around gleaming cityscapes doing calculus in their heads while the un-engineered lower classes battle over the scraps and rely on government-funded feed pellets and VR.

Yet the latest tech isn’t walled off from the middle and working classes. Take the smartphone for example. 20 years ago, only the likes of Zack Morris and Pablo Escobar (yeah, I know it’s from Narcos) had mobile phones. Today, there are nearly 3 billion smartphones in circulation worldwide and by 2020, there’ll be over 6 billion. That’s space-age technology—palm sized devices that contain all the world’s knowledge and wisdom and information—and it’s available to almost half the world, from Nigeria to Nice to New Zealand.

CRISPR itself is quite cost effective and accessible, and not just to research centers and universities. DIYers are putting together CRISPR labs at home for $1000 and using software to design custom genetic sequences. A recent Kickstarter offered CRISPR kits that fit on your kitchen table for under $200. I expect it’ll only get easier and cheaper.

We’re a long way away from in vivo genetic editing of large adult mammals. There are major hurdles to that, like that fact that you don’t immerse yourself in a CRISPR bath that permeates your tissues. You can’t swallow a “CRISPR pill” that modifies all your adult DNA. It doesn’t “know” where to go without you delivering it to the right tissues.

But editing human embryos shortly after conception is a viable way of altering the genetic makeup of an (eventual) adult. The Chinese are beginning trials in human embryos. Pretty soon, parents will be able to select the traits they desire in their children, or even send CRISPR-ized nanobots into the placenta with editing instructions. I fully expect the first human to break a 9 second 100m dash will be a CRISPRed Chinese guy.

Still, maybe the biggest hurdle of all is our incomplete knowledge. We need broader genetic datasets, incuding genomes from different ethnicities, to untangle and identify the SNPs that cause traits (especially complex ones) and conditions. At this point, we just don’t know if (or where) many “genes for” this condition or that trait exist.

Interesting stuff, indeed! The future is here (kinda). I’m both excited and a bit uneasy about what’s to come. I’m sure there will be a process of trial and error, good, bad, and unforeseen consequences. But I’m banking on it being good overall.

So crazy! Yes, perhaps wayyyyyyyyy down the line, we’ll be able to modify our genome to make us hyperproductive, content, disease-free super beings, but I don’t see that happening any time soon. So most likely for all of our lifetimes, living Primal is going to be a best bet at living the best life possible.

Ah, one can dream. A future where we can eat whatever we want with reckless abandon does sound kind of nice. Like that movie with Meryl Streep where she goes to heaven and can eat as many pies as she wants without gaining a pound. Heaven on earth is only a couple thousand SNP modifications away…

Jason Bourne…Nocona makes a good point. Though if you are a fan of the franchise it’s more Aaron Cross in the Bourne Legacy where they built super spies in the lab. And you can google articles that discuss the reality of that science. It will so fascinating to see where we go….

My brain goes weird places sometimes. I see “CRISPR” and I pronounce it “crisper,” like the vegetable crisper in the refrigerator. Then I spend half the article trying not to laugh at the image of crispy lettuce editing DNA. That being said, the CRISPR sounds very interesting. I clicked on the article about the Chinese trials, and they’re working to edit T cells in lung cancer patients, so that the cancer can’t shut down the T cells, enabling the patient’s own immune system to fight the cancer. That sounds very promising indeed.

What the heck happened to you, Mark? First you’re defending GMOs, then you’re questioning whether EMFs are harmful, and now you’re a transhumanist? Wasn’t it just last year you were telling Dave Asprey that you’re a luddite? I don’t like where your site and your personal philosophy are going. I don’t even think of you as the same guy anymore.

DIY CRISPR kits for some kid in his basement? How is this positive? Look what (probably irreparable) damage GMOs have already done to the environment. Unbridled genetic experimentation is going to be a dystopian disaster. You can’t just brush that off because you know a term like cyberpunk. That’s a real concern.

Why wouldn’t you ultimately want to embrace technology that could eventually eliminate diseases that cause immeasurable suffering worldwide? Technology and innovation always have the potential to produce horrific outcomes. As tech advances, we’re all going have to put a little faith in humankind that we won’t obliterate ourselves. It’s almost happened before. That’s why there’s a call for an international ethics committee for CRISPR Cas9.

You obviously read Mark’s site. He’s a realist. If you want to live in a first-world industrial society, embracing technology is usually the best approach. You don’t have to live it. But you have to learn to live among it, otherwise the divide between the two groups becomes wider and real problems arise.

DIY kits just further the hacking and DIY community that’s led to some of the best products and discoveries. Who knows what those home DIY CRISPR hackers will discover—perhaps a targeted method to cure cancer…

I can give you a million reasons not to embrace technology and gene editing as a cure to “immeasurable suffering worldwide:”

Said suffering was mostly caused by “brilliant technological innovations” such as hits like:

1. Pesticides like Agent Orange, DDT, and glyphosate
2. Abuse of antibiotics and oversanitization that have thrown the human microbiome out of whack (despite their benefits in saving lives)
3. Nuclear radiation from atomic weapons and nuclear power plants (from Hiroshima to Fukishima)
4. Microwave radiation (radar, microwave ovens, cell phones, routers, etc.)
5. Fluoridation of the water supply, among many other pollutants that make tap water unsafe
6. Countless industrial chemicals polluting our water supply, once again making tap water undrinkable and many bodies of water untouchable
7. Countless pharmaceuticals known to kill hundreds of thousands of people a year
8. Genetically modified clones in the food supply that have caused damage to the microbiome and possibly the DNA of humans and animals worldwide

So you think getting in there and jiggering even more with the fundamental code of life is going to fix the damage we’ve done? It’s like a hilarious comedic routine of the kids getting a frisbee stuck in a tree, then throwing a tennis racket to knock the frisbee out, followed by a basketball to unhinge the racket, the neighbor’s cat to free the basketball, a small child to retrieve the cat, and so on and so forth. Or the elderly matron who accidentally ingested a fly? Let’s skip to the punchline: rumor has it she swallowed a horse and well—she died of course.

If you and I are future archetypes of these two approaches, then that’s where the two groups already are inevitably going to diverge. I thought this so-called Primal movement was about reestablishing our original relationship with nature and the environment, and emulating as much as possible the lifestyle that humans have naturally developed to effect the healthiest, happiest coexistence possible with the Earth. But what you’re suggesting is more of the same selfish attitude we’ve had in these last several resource-pillaging and environment-modifying centuries, and it will only effect further separation from it as we appropriate more and more discrete materials from it with ham-fisted tunnel vision focused on our own advancement.

I’m not an environmentalist, either. I’m not saying to put the environment first, really. I just recognize that almost all of the things that are best for humans just so happen to look like environmentalism. I refuse to ignore that any longer.

I am not optimistic. Humans are lazy – and, the idea of home-brewed genetic experiments scares the crap out of me. And, if we are trying to engineer a super-race (and, I guarantee – it will happen) – welcome to Nazi Germany all over again.

I will take my chances on eating right, exercising right, enjoying life and living until it is my time!

I find this very disturbing. We really need to stop playing God. That being said since we are not God I see a lot of other problems arising. I don’t think they will be able to perfect it in a way to not cause something else to go wrong. I like the idea of fighting viruses and other health related problems though and I think they should just stick with that.

This article is rather glib and lacks the wisdom and balance that characterises Mark’s usual offerings. I agree that there is room for some optimism regarding crispr tech, but the treatment of the attendant risks, in this article, just doesn’t do justice to their seriousness at all. Eugenic utopian idealism wrecked havoc in the 20th century. We have good reason to be extremely careful and just a bit sceptical about whether and how this will be a long term benefit to human beings in general, and whether that benefit is worth the risks.

Will there be 2 Olympics? One for sustainable grown people and one for genetically modified people? 2 types of baseball fields – one for organically grown humans and one for people designed to hit a baseball further so that homeruns are still an accomplishment? Will there be 2 university systems – one for naturally human people and one for intelligently designed people? Will natural humans be eligible for all jobs or will they be discriminated against? Will natural humans still have access to medical care? If a condition can be cured or improved by CRISPR, will medical authorities be allowed for force the procedure on people whether they want it or not? Will a natural person be denied insurance, medicare, medicaid, or welfare if they decline to be “adjusted?” Will CRISPR ignore the fact of environmental affects on epigenetic expression and presume all genetic disease markers must be revised according to some lobbyist’s ideas of how the human condition should proceed? Can CRISPR adjusted genes be down-regulated by too many Twinkies? Most importantly, will Dick Cheney live forever?

Don’t shoot the messenger folks and don’t bury your head in the sand. I’m guessing none of the negative comments about the potential for genetic engineering are from people who have spina bifida or down’s syndrome etc. You can rail against technological and medical advances or you can understand that it’s coming and support efforts to regulate it so that its used to do good, not harm. Yes, the potential future is both fascinating and scary. Mankind has a potential that ranges from turning this planet into an eden or destroying it. Futurists tend to agree we have a 50 / 50 chance for tipping either way. That’s why we need to have a global perspective and work as a global community.

The way the pharmaceutical industry is regulated? At least that only impacts the person taking it, not their children. If we had any firm concept of how genetics works this would be less alarming. I’m surprised Mark brushes off the concept of genetic diseases as simple and well understood. He’s read “The Sports Gene” which does a great job of illustrating exactly where we are in our understanding of the impact of genetics. Bottom line, we aren’t very far along. If I had down’s syndrome, etc. then maybe I would sign up for the trials, I’ll definitely give you that, but I’d want to know that we aren’t at all certain it would work and we aren’t aware of what other changes I would experience.

The problem is drug therapy may impact potential offspring. For example, most if not all vaccine info states there has been zero testing on reproductive capacity/fertility. Just as there has been zero testing for potential genetic mutations or carcinogenic potential for any vaccine used today. So we don’t really know.

We are already altering our genes through too many drugs and bad food. Isn’t the primal lifestyle is all about altering our genes but in a good way, correct?

I’ve been away from MDA for a while, been focussed in other areas. I find this post somewhat alarming to say the least – has Mark been kidnapped in my absence, genetically modified on the QT? Life isn’t about perfection, I thought life was about living the experience, the challenges, the highs, the lows, the soul learning.

I’m with Mark on this. Every significant advance to human technology has brought both good and bad. Think vaccines, automation, tractors, the telegraph, the bow and arrow. And in the long run the good outweighs the bad. We share in our own evolution. Let’s get our heads around the possibilities here and find good uses for CRISPR rather than running away from it and leaving all the choices to people we may neither like nor trust.

I’m optimistic about the possibilities as well, but you identify a crucial point when speaking about our incomplete knowledge. When this hurdle is passed, we could do all the great things you talk about. Only, we are already starting, and ultimately I think with more ignorent than complete knowledge. We have proven earlier on with GMO’s that we have the inclination to think we understand something which then appears to be much, much more complex than we thought. Only by then we’re already stuck with the gigantic problems we’ve created (and even then most of us keep on believing we understand it all). I see little reason to believe we won’t make this same mistake with CRISPR.

Boh. Cool and exciting, I don’t know. Creepy, yes. But then, I err on the side of Zen, where the lotus flower bursts forth from the mud, and the lesson to be learned is compassionate acceptance of both the beauty of life and it’s dark sides. Suffering exists. That’s the first of the Buddha’s 4 Nobile Truths. So accept it, instead of trying to push it away all the time.

Scary stuff here. I have to agree with the naysayers on this. Put me down as a NO vote, that is if I had a vote, which of course I do not. The modified future is coming and there is nothing anyone can do to stop it. We have kids in basements with computers all over the world hacking all our info and there is very little we can do to protect ourselves. Heck governments can’t even protect themselves. Now we have so called DIYers setting up little home gene splicing labs experimenting on God only knows what. The real scientists maybe working on cures and benefits but it’s the Dr. Frankenstiens and North Koreans that worry me.

Many tools can be used for good or ill. As a biologist I am excited about any steps we can take to reduce suffering, using these technologies and those we develop in the future. Of course we must have a public debate about peoples’ concerns and the implications of any new technology.
However, every time there is a new invention people get concerned that society will deteriorate and bad things will happen but, more often than not, we all end up using those technologies (or their offspring) in our everyday lives without even thinking twice.
These are indeed exciting times.

If we don’t know enough about the human body to correctly and completely predict the impact of pharmaceuticals, or heck even diet, on the human body, why would we assume we know enough to start playing with genes? At least pharmaceutical and dietary mistakes aren’t passed on to the next generation. I see the appeal in treating disease, but The Sports Gene (where I assume the myostatin idea came from) makes it clear that we don’t understand genetics well enough to identify the precise impacts each gene has. If I had terminal cancer with no other option and weeks to live, I might sign up. Other than that, not a chance.

I’m a human embryologist involved in some of these issues over the past 30 years – and just wanted to praise this excellent, accurate and balanced discussion. Its really quite rare to see. Great job Mark. Please keep up the good work.

The dog in the article is a whippet with a genetic anomaly which is relatively common in Whippets.
I think tinkering with genes is unwise until we really understand what we are doing and get the moral implications right.

I don’t know. The drug cartel may have something to say about this future if it points to their products becoming obsolete. The vaccine cartel will surely not want us to be genetically able to resist disease. They’ve got loads of vaccines in the pipeline worth billions for every disease under the sun and plenty more they’re still making up!

no amount of genetic “perfection” will negate the need for a healthy lifestyle. It’s like designing a better car, and then using the reasoning that you can now put crappy oil in in and not maintain it – justifying that it still has the performance of an old cheap car this way.

Actually, just like the high end sports car, it may indicate that even more frequent and careful maintenance will be needed as a result of having a the higher performance potential – switching on or enhancing one gene, trades off against another – want to run faster ?, you may have to trade off disease resistance for example.

We see this in dog breeding – some dogs are particularly good at certain skills, but it comes as a trade off for that particular breed in the form of negative side effect traits.

The reality is that there are limits to what can be done with biological machines – if we want more “performance” we could be talking non-biological humans, but then what exactly is that – as I tick the box here to submit this comment which says “I’m not a robot” – how long will that hold into the future ?